The object of the present invention is the development of a process which provides a stable, solution of theophylline in pure water without the introduction of foreign solubilizers and which has good solubility under neutral conditions. The invention also includes the novel compositions prepared.
The classical solution to this problem at present is the process for the production of aminophyllines. These compounds are formed by dissolving pure theophylline in strongly alkaline, aqueous solution of aliphatic amines. The most important way of carrying out this process is that for the production of the aminophylline Pharmacopeia V (see also, the United States Pharmacopeia XVIII, pages 33-34). Thereby, pure theophylline is dissolved in an aqueous solution containing 20 parts by weight of ethylene diamine (pH about 10). However, all of these solutions are chemically unstable because of their high dependency on pH. In such solutions, even the carbonic acid from the air can cause a precipitation of the pure theophylline. This is also true in the stomach due to the free hydrochloric acid. Besides, the ethylene diamine irritates the skin, especially the mucous membrane, which can even lead to dermatitis. With alkaline solutions, besides it is very problematical that mixtures are formed with other medicines because of the precipitation of the dissolved materials. Likewise, because of the strongly alkaline solution, the blood vessels are irritated in the injection of the solution.
All of these defects are eliminated by the use of the process of the present invention as well as by the use of the products produced thereby.
This invention therefore signifies a true advance because the thus obtained aqueous solution is not only chemically stable, but is also practically pH insensitive.